By Michelle Jaffee
Muscle weakness or pain is common in everything from bacterial infections to Alzheimer’s disease to COVID. Now, University of Florida researchers and collaborators at Washington University School of Medicine in St. Louis have identified what appears to be a key mechanism: In preclinical studies, they’ve shown how brain inflammation caused by infection or chronic disease triggers the release of a protein that travels to other parts of the body to impair muscle function.
The findings, reported July 12 in Science Immunology, could pave the way for new therapeutic targets.
“This research shows how studying fruit flies can improve our understanding of brain-muscle communication in disease, potentially leading to new treatment options for several debilitating conditions,” said co-author Diego Rincon-Limas, Ph.D., an MBI researcher and an associate professor of neurology at the University of Florida.
The international research team, led by Aaron Johnson, Ph.D., of WashU and postdoctoral researcher Shuo Yang, Ph.D., used multiple models of central nervous system stress in fruit flies and mice to better understand how inflammatory signals in the brain are relayed to skeletal muscle. The fruit fly portion of the study, led by Johnson and Rincon-Limas, indicated that brain inflammation activates a sequence of events involving a protein called Upd3 in fruit flies, which acts similarly to the human cytokine IL-6.
“We are interested in understanding the very deep muscle fatigue that is associated with some common illnesses,” said Johnson, an associate professor of developmental biology. “Our study suggests that when we get sick, messenger proteins from the brain travel through the bloodstream and reduce energy levels in skeletal muscle. This is more than a lack of motivation to move because we don’t feel well. These processes reduce energy levels in skeletal muscle, decreasing the capacity to move and function normally.”
The fruit fly experiments showed that bacterial infections within the brain lead to an increase in harmful molecules called reactive oxygen species, and that these molecules trigger a signaling pathway that produces Upd3, affecting mitochondria and impairing muscle function. Similar results were seen in a fly model of Alzheimer’s created by Rincon-Limas.
“We believe this is the first case where a brain-produced messenger protein has been found to travel to exert control over muscle function,” said co-author Deepak Chhangani, Ph.D., an assistant scientist in UF’s department of neurology.
Read the paper in Science Immunology.
Read the WashU news release.
